Hydroxychloroquine, a drug prescribed to treat rheumatoid arthritis and lupus, has been touted as a possible treatment for COVID-19, leading to an influx of studies on the subject as well as nationwide shortages of the drug. However, another study has come out rejecting the notion that hydroxychloroquine is a useful drug for COVID-19, with the authors concluding that “treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality.”
“Although randomized double-blind clinical trials are the optimal study design, given the urgent need to respond to the COVID-19 pandemic in New York an observational study was implemented to evaluate the clinical outcomes and adverse effects associated with hydroxychloroquine and azithromycin therapies for COVID-19,” the study authors explained. “The aim was to understand prescribing patterns of hydroxychloroquine and azithromycin in hospitalized patients with COVID-19 and the association of these drugs with mortality and possible adverse events.”
A random sample of patients with laboratory-confirmed COVID-19 admitted to one of 25 New York hospitals between March 15 and 28, 2020, were assessed. Medical records provided data on medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events. Final follow-up was performed on April 24. Patients received one or both of hydroxychloroquine and azithromycin, or neither. In-hospital mortality was the primary study outcome, with secondary outcomes including cardiac arrest and abnormal electrocardiogram findings (arrhythmia or QT prolongation).
Hydroxychloroquine Alone or With Azithromycin Not Beneficial
Final analysis included 1,438 hospitalized COVID-19 patients (median age, 63 years; 59.7% were male). Patients receiving hydroxychloroquine, azithromycin, or both were more likely than controls to have diabetes, respiratory rate >22/min, abnormal chest imaging findings, O2 saturation <90%, or aspartate aminotransferase > 40 U/L. The collective in-hospital mortality rate was 20.3%; for patients receiving hydroxychloroquine plus azithromycin, 25.7%; hydroxychloroquine alone, 19.9%; azithromycin alone, 10.0%; and neither drug, 12.7%. When using adjusted Cox proportional hazards models, when using patients receiving neither drug as the reference, mortality did not largely differ for patients receiving hydroxychloroquine plus azithromycin (hazard ratio [HR]=1.35; 95% confidence interval [CI], 0.76 to 2.40), hydroxychloroquine alone (HR=1.08; 95% CI, 0.63 to 1.85), or azithromycin alone (HR=0.56; 95% CI, 0.26 to 1.21). When using logistic models, patients receiving hydroxychloroquine plus azithromycin, compared to those receiving neither drug, were more likely to suffer cardiac arrest (adjusted odds ratio [aOR]=2.13; 95% CI, 1.12 to 4.05); this correlation was not observed in patients receiving hydroxychloroquine alone (aOR=1.91; 95% CI, 0.96 to 3.81) or azithromycin alone (aOR=0.64; 95% CI, 0.27 to 1.56). Adjusted logistic regression models yielded no significant differences in relative likelihood to present abnormal electrocardiogram findings.
The study is limited by its observational design, the researchers noted in JAMA.
“Clinical trials remain needed to provide definitive causal evidence of the effect of hydroxychloroquine and azithromycin on mortality, while also providing an opportunity to more finely control baseline patient severity and the dose and timing of drug administration. Nonetheless, the findings of the present study should be considered in concert with recent COVID-19 treatment guidelines from the National Institutes of Health and Infectious Diseases Society of America as well as the statement regarding safety concerning use of hydroxychloroquine from the US Food and Drug Administration,” they stated.